This is a competitive renewal application for Dr. Glen Hanson's Senior Scientist Award. Dr. Hanson is a tenured professor in the Department of Pharmacol. &Tox. at the University of Utah with more than 20 years experience in drug abuse research resulting in important contributions to our understanding of the short- and long-term effects of psychostimulants on brain monoaminergic and neuropeptide systems. Dr. Hanson's K05 award (beginning in 1998) has relieved him from heavy teaching and committee responsibilities, allowing Dr. Hanson to devote >75% of his professional time to substance abuse/addiction research-related endeavors. Activities supported by his K05 award resulted in: (i) ~57 peer-reviewed scientific publications;(ii) >90 abstracts presented at scientific meetings;(iii) an appointment as the director of NIDA's Division of Neuro-science and Behavioral Research (2000-2001);(iv) becoming the acting Director of the National Institute on Drug Abuse (2001-2003);(v) an appointment as the director of the Utah Addiction Center (2003-present);and (vi) becoming a senior advisor to the director of NIDA (2003-present). Renewal of Dr. Hanson's K05 will permit him to direct research to test the following principal hypotheses: (i) the functional output of the striato-nigral pathway is increased by administration of low doses of methamphtamine and unaffected by administration of high doses of this drug;(ii) expression of a 2nd , but not the 1st , component of an acute response of the vesicular monoamine transporter-2 is linked to the occurrence of phenylethylamine-induced monamine neurotoxicity;and (iii) there are related mechanisms fundamental to the refractoriness of the nigrostriatal dopamine pathway to methamphetamine-induced neurotoxicity in: adolescent;previously lesioned;and tolerant, rats. Continuation of his K05 will allow Dr. Hanson to develop expertise in technologies that will substantially further his research efforts, such as: (i) subcellular fractionation;(ii) Western blotting and immunoprecipitation protein characterization;(iii) rotating disk electrode voltammetry;and (iv) self-administration contingency paradigms. In addition to research projects, the K05 support will allow Dr. Hanson to direct efforts to create interdisciplinary research teams to conduct drug abuse and translational research. Finally, this award will permit Dr. Hanson to continue mentoring inexperienced researchers at the under-graduate, graduate, postdoctoral and young faculty levels, to assist them in their scientific development.